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Simple mediation model of genetic susceptibility to obesity. Illustration of a simple mediation model in which genetic susceptibility to obesity (independent variable X) influences an obesity trait (dependent variable Y) directly (c’) or indirectly through a mediator M. The direct and indirect effects add to yield the total effect (c) of X on Y. The paths of the model labeled a, b, c, and c’ are estimated using the three regression equations represented in the figure. The indirect effect or mediated effect of X on Y through M is quantified as the product of a and b (ab).
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Background: Obesity results from complex interactions between genetic susceptibility to weight gain and poor eating and lifestyle behaviors. The approach that has been traditionally used in genetics to investigate gene-environment/lifestyle interaction in obesity is based on the concept of moderation, or effect modification. Another approach called...
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Noncommunicable diseases (NCDs) are influenced by the interplay between genetics and environmental exposures, particularly diet. However, many healthcare professionals, including nutritionists and dietitians, have limited genetic background and, therefore, they may lack understanding of gene–environment interactions (GxEs) studies. Even researchers...
Citations
... With the advancement of genomics research, several mediation and interaction studies have analyzed relationships between dietary patterns and obesity genes. Mediation analyses aim to identify how an intermediate variable may explain the effects of an observed association [3], whereas interaction studies aim to assess the modifying effects of an intermediate variable on the effects between an exposure on an outcome [4]. In other words, mediation studies may be useful for identifying targets for intervention, whereas interaction studies may identify subgroups that are responsive to a particular intervention [4]. ...
... Mediation analyses aim to identify how an intermediate variable may explain the effects of an observed association [3], whereas interaction studies aim to assess the modifying effects of an intermediate variable on the effects between an exposure on an outcome [4]. In other words, mediation studies may be useful for identifying targets for intervention, whereas interaction studies may identify subgroups that are responsive to a particular intervention [4]. Prior studies have shown that genetic risk to obesity was mostly mediated by eating behaviors [5] although the genetic susceptibility to obesity was also mediated by other factors such as gray matter volume [6,7], early life stress [8], leptin levels [9], or education, physical activity, conscientiousness, and depressive symptoms [10]. ...
Objective: The study's objective was to examine whether adherence to three plant-based dietary indices (PDIs) mediated or moderated genetic susceptibility to obesity.
Methods: Baseline participants were 7037 adults (57% women, aged 55.6 ± 7.7 years) from the CARTaGENE cohort of Quebec adults. Two polygenic risk scores for BMI (PRS-BMI), 92 single-nucleotide polymorphisms and 2 million single-nucleotide polymorphisms, and three plant-based scores were calculated (overall, healthy, and unhealthy). Follow-up participants were 2258 adults with data on obesity outcomes, measured 6 years later. General linear models were used to examine the relationships between PRSs and PDI scores on obesity outcomes. Causal mediation analyses were conducted to assess mediation and interaction models.
Results: The overall- and healthy-PDIs and PRSs were significantly associated with obesity outcomes. Adherence to PDIs did not mediate or moderate genetic susceptibility to obesity. Associations between PRSs and obesity outcomes were partly mediated by meat intake cross-sectionally and whole grains intake among males both cross-sectionally and longitudinally. Higher meat intake had a positive association with obesity outcomes, whereas higher whole grains intake had an inverse association.
Conclusions: These findings suggest that components of a plant-based diet and a shift away from animal products, specifically meat, might be beneficial for nutrition interventions, particularly among individuals with higher genetic risk of obesity.
... To further explore this interaction, a mediation analysis was performed, which revealed that LDH significantly mediated the effect of anisocytosis on SaO 2 by 41%. Mediation analyses are a very interesting approach, since they provide insightful information about to what extent a variable affects another and can occur simultaneously with an interaction [49]. This effect can be direct, such as the effect of anisocytosis on SaO 2 (anisocytosis → SaO 2 ), or indirect, the same effect but mediated by LDH (anisocytosis → LDH → SaO 2 ). ...
Viral infections activate the innate immune response and the secretion of inflammatory cytokines. They also alter oxidative stress markers, which potentially can have an involvement in the pathogenesis of the disease. The aim of this research was to study the role of the oxidative stress process assessed through lactate dehydrogenase (LDH) on the severity of COVID-19 measured by oxygen saturation (SaO2) and the putative interaction with inflammation. The investigation enrolled 1808 patients (mean age of 68 and 60% male) with COVID-19 from the HM Hospitals database. To explore interactions, a regression model and mediation analyses were performed. The patients with lower SaO2 presented lymphopenia and higher values of neutrophils-to-lymphocytes ratio and on the anisocytosis coefficient. The regression model showed an interaction between LDH and anisocytosis, suggesting that high levels of LDH (>544 U/L) and an anisocytosis coefficient higher than 10% can impact SaO2 in COVID-19 patients. Moreover, analysis revealed that LDH mediated 41% (p value = 0.001) of the effect of anisocytosis on SaO2 in this cohort. This investigation revealed that the oxidative stress marker LDH and the interaction with anisocytosis have an important role in the severity of COVID-19 infection and should be considered for the management and treatment of the oxidative phenomena concerning this within a precision medicine strategy.
... Obesity holds its roots in a complex lifestyle-gene interaction, deeply interconnected to epigenetic alterations. Since preventive measures are often reported to fail, interest in new approaches is rising, for example in the field of nutraceuticals using antioxidants to overcome acute oxidative stress [58,59]. Similarly, ROS are key players in development of low-grade inflammation, which in turn is involved in the physiopathology of polycystic ovary syndrome (related to insulin-resistance, immune dyscrasia and much more), as well as in metabolic syndrome-related manifestation, as atherosclerosis, hypertension, and T2D: hence, a profound understanding of the link between onset of such conditions and their genetic bases (for instance, at the level of the histone code and overall chromatin organization) could be reflected in discovery of new targets and development of new therapies aiming at ameliorating patients' life conditions [60,61]. ...
Cell genome integrity is continuously threatened by various sources, both endogenous and exogenous. Oxidative stress causes a multitude of damages, severely affecting cell viability, fidelity of genetic information inheritance, and determining profound alterations in gene expression. Epigenetics represents a major form of gene expression modulation, influencing DNA accessibility to transcription factors and the overall nuclear architecture. When assessing the stress-induced epigenome reprogramming, widely diffused biochemical and molecular approaches commonly fail to incorporate analyses such as architectural chromatin alterations and target molecules precise spatial localization. Unveiling the significance of the nuclear response to the oxidative stress, as well as the functional effects over the chromatin organization, may reveal targets and strategies for approaches aiming at limiting the impact on cellular stability. For these reasons, we utilized potassium bromate treatment, a stressor able to induce DNA damages without altering the cellular microenvironment, hence purely modeling nuclear oxidative stress. By means of high-resolution techniques, we described profound alterations in DNA and histone epigenetic modifications and in chromatin organization in response to the reactive oxygen species.
... There is currently insufficient evidence to support any specific weight management regimen for the treatment of obesity in middle-aged and older adults. The most successful program so far is a combination of behavioral therapy and lifestyle modification therapy [5,6]. But because these programs require family involvement and changes in established eating or activity habits, they are often intolerable and easily dropped out [6]. ...
Objective:
To explore the best treatment of obesity in middle and old age.
Methods:
80 obese patients in our hospital from January 2020 to December 2021 were randomly divided into the control group and the intervention group according to the numerical table method. The control group was treated with lifestyle intervention, while the intervention group was treated with dapagliflozin combined with lifestyle intervention. The effects of body weight, body mass index (BMI), waist circumference, and blood lipids (LDL, HDL, TC, and TG) were measured and compared. Anxiety and depression scores were assessed using the 2018 Revised Anxiety and Depression Scale.
Results:
There were no significant differences in body weight, BMI, and waist circumference between the control group and the intervention group before treatment. After treatment, the weight, BMI, and waist circumference of the intervention group were lower than those of the control group, and the difference was statistically significant (P < 0.05). After treatment, LDL, TC, and TG in the two groups were decreased, and HDL was significantly increased (P < 0.05). After treatment, the blood lipid level in the intervention group was significantly lower than that in the control group (P < 0.05). Anxiety and depression symptoms improved in both groups, and there were no serious adverse effects.
Conclusion:
Dapagliflozin in combination with a lifestyle intervention effectively and safely treats excess weight in middle-aged and older adults, reverses obesity-related markers, and improves psychological symptoms. Its curative effect is better than that of using lifestyle intervention alone.
In numerous brain structures, insulin signaling modulates the homeostatic processes, sensitivity to reward pathways, executive function, memory, and cognition. Through human studies and animal models, mounting evidence implicates central insulin signaling in the metabolic, physiological, and psychological consequences of early life adversity. In this review, we describe the consequences of early life adversity in the brain where insulin signaling is a key factor and how insulin may moderate the effects of adversity on psychiatric and cardio-metabolic health outcomes. Further understanding of how early life adversity and insulin signaling impact specific brain regions and mental and physical health outcomes will assist in prevention, diagnosis, and potential intervention following early life adversity.
